A variety of physiological events are directly or indirectly under the control of catecholamine hormones secreted by the adrenal glands, or neuronal cells comprising the sympathetic nervous system. The two most widely studied catecholamines are epinephrine and norepinephrine. Epinephrine cause a dramatic elevation in blood pressure arising from arteriolar vasoconstriction, and a concomitant rise in heart rate and cardiac output. Norepinephrine also influences blood pressure, but by a mechanism independent of cardiac output. Rather, norepinephrine increase blood pressure by increasing peripheral vascular resistance.
There is evidence that suggests that abnormally high levels of epinephrine and norepinephrine are responsible for causing hypertension. The latter disease is associated with dysfunction of arterial blood pressure regulation. One means whereby elevated catecholamine levels arise in an organism is their production by tumors, particularly tumors of the adrenals, pheochromocytomas. The latter is of chromaffin tissue origin and, generally, spontaneously secretes catecholamines into the blood.
In addition to their effects on blood pressure, epinephrine and norepinephrine also affect both catabolism and lipid metabolism.
In light of the link between epinephrine and norepinephrine with hypertension and adrenal tumors, it is desirable to have a reliable assay whereby fluctuations in these hormones can be monitored, and hence, utilized in diagnosing the diseases. Several direct tests for detecting catecholamines in physiological fluids are presently in use. These involve chemical analysis, which for the most part is time consuming, insensitive, or unreliable. Indirect tests for catecholamines rely on detecting substances that are secreted along with catecholamines into the blood, and thus their presence can be correlated with circulating catecholamine levels.
Indirect tests for catecholamines are premised on the fact that, prior to being secreted into the blood, catecholamines are stored in vesicles that contain, in addition to catecholamines, a variety of proteins. One such protein, chromogranin A, has been the focus of efforts to establish a reliable indirect assay. While chromogranin A can be satisfactorily assayed in animals other than man, to date attempts at establishing a clinically useful assay for humans have revolved around detecting chromogranin A using microcomplement fixation techniques; and for the most part, these efforts have proved futile.
Considering the role that catecholamines play in the pathogenesis, or symptomatology of particular diseases, it would be of value to have a reliable assay that could be used in a clinical setting to detect the presence of chromogranin A in bodily fluids.